Cytotoxic effect of uranium dioxide on rat alveolar macrophages.

Alveolar macrophages obtained by bronchial lavage were used to assess the response of these cells to cultivation in media containing increasing concentrations of particulate UO2. The characteristic time course of uranium effects on alveolar macrophages was determined by analyzing cell viability and incorporation of uranium particles. This study reveals the ability of alveolar macrophages to phagocytize uranium particles despite the high toxicity the metal exerts on cell membranes. However, lethal effects soon become evident. Ultrastructural analysis showed uranium particles confined within membrane bound vacuoles or free in the cytoplasm. Marked ultrastructural alterations consistent with cell death were frequently observed. The elimination of the first biological barrier hinders the scavenging of particulate contaminants in alveolar spaces, thus favoring the translocation to target organs.